Daniel Y. Kimberg

Arterial spin labeling perfusion fMRI with very low task frequency

Functional magnetic resonance imaging (fMRI) has become the most widely used modality for visualizing regional brain activation in response to sensorimotor or cognitive tasks. While the majority of fMRI studies have used blood oxygenation level‐dependent (BOLD) contrast as a marker for neural activation, baseline drift effects result in poor sensitivity for detecting slow variations in neural activity. By contrast, drift effects are minimized in arterial spin labeling (ASL) perfusion contrast, primarily as a result of successive pairwise subtraction between images acquired with and without labeling. Recent data suggest that ASL contrast shows stable noise characteristics over the entire frequency spectrum, which makes it suitable for studying low‐frequency events in brain function. The present study investigates the relative sensitivities of ASL and BOLD contrast in detecting changes in motor cortex activation over a spectrum of frequencies of experimental design, where the alternating period between the resting state and activation is varied from 30 s up to 24 hr. The results demonstrate that 1) ASL contrast can detect differences in motor cortex activation over periods of minutes, hours, and even days; 2) the functional sensitivity of ASL contrast becomes superior to that of BOLD contrast when the alternating period between the resting state and activation is greater than a few minutes; and 3) task activation measured by ASL tends to have less intersubject variability than BOLD contrast. The improved sensitivity of the ASL contrast for low task frequency and longitudinal studies, along with its superior power in group analysis, is expected to extend the range of experimental designs that can be studied using fMRI. Magn Reson Med 49:796–802, 2003.

Neural correlates of cognitive efficiency

Since its inception, experimental psychology has sought to account for individual differences in human performance. Some neuroimaging research, involving complex behavioral paradigms, has suggested that faster-performing individuals show greater neural activity than slower performers. Other research has suggested that faster-performing individuals show less neural activity than slower performers. To examine the neural basis of individual performance differences, we had participants perform a simple speeded-processing task during fMRI scanning. In some prefrontal cortical (PFC) brain regions, faster performers showed less cortical activity than slower performers while in other PFC and parietal regions they showed greater activity. Regional-causality analysis indicated that PFC exerted more influence over other brain regions for slower than for faster individuals. These results suggest that a critical determinant of individual performance differences is the efficiency of interactions between brain regions and that slower individuals may require more prefrontal executive control than faster individuals to perform successfully.

Localizing interference during naming: convergent neuroimaging and neuropsychological evidence for the function of Broca's area.

To produce a word, the intended word must be selected from a competing set of other words. In other domains where competition affects the selection process, the left inferior frontal gyrus (LIFG) responds to competition among incompatible representations. The aim of this study was to test whether the LIFG is necessary for resolution of competition in word production. Using a methodological approach applying the same rigorous analytic methods to neuropsychological data as is done with neuroimaging data, we compared brain activation patterns in normal speakers (using fMRI) with the results of lesion-deficit correlations in aphasic speakers who performed the same word production task designed to elicit competition during lexical selection. The degree of activation of the LIFG in normal speakers and damage to the LIFG in aphasic speakers was associated with performance on the production task. These convergent findings provide strong support for the hypothesis that the region of cortex commonly known as Brocas area (i.e., the posterior LIFG) serves to bias competitive interactions during language production.

Anterior temporal involvement in semantic word retrieval: voxel-based lesion-symptom mapping evidence from aphasia

Analysis of error types provides useful information about the stages and processes involved in normal and aphasic word production. In picture naming, semantic errors (horse for goat) generally result from something having gone awry in lexical access such that the right concept was mapped to the wrong word. This study used the new lesion analysis technique known as voxel-based lesion-symptom mapping to investigate the locus of lesions that give rise to semantic naming errors. Semantic errors were obtained from 64 individuals with post-stroke aphasia, who also underwent high-resolution structural brain scans. Whole brain voxel-based lesion-symptom mapping was carried out to determine where lesion status predicted semantic error rate. The strongest associations were found in the left anterior to mid middle temporal gyrus. This area also showed strong and significant effects in further analyses that statistically controlled for deficits in pre-lexical, conceptualization processes that might have contributed to semantic error production. This study is the first to demonstrate a specific and necessary role for the left anterior temporal lobe in mapping concepts to words in production. We hypothesize that this role consists in the conveyance of fine-grained semantic distinctions to the lexical system. Our results line up with evidence from semantic dementia, the convergence zone framework and meta-analyses of neuroimaging studies on word production. At the same time, they cast doubt on the classical linkage of semantic error production to lesions in and around Wernickes area.

Modulation of task-related neural activity in task-switching: an fMRI study

Task-switching paradigms, in which subjects are typically asked to switch between different S-R mappings, can be considered operationalizations of executive control. Such paradigms are therefore potentially useful in investigating the neural bases of control functions. Here, we present the results of an fMRI study intended to examine two separable components of task-switching: preparation, and the residual shift cost identified by Rogers and Monsell [13]. In analyses restricted to functionally identified regions of interest, we found robust evidence of greater activity for switch trials, compared to repeat trials. This pattern was present both at the time of stimulus presentation and prior to the switch trial. In analyses of the entire brain, we were able to identify one area in the superior parietal lobule that was active during switching but was not part of the apparent network of task-related regions. We conclude that switch trials are neurally distinct from repeat trials in eliciting generally greater neural activity both before and during the performance of a trial.

Power in Voxel-based Lesion-Symptom Mapping

Lesion analysis in brain-injured populations complements what can be learned from functional neuroimaging. Voxel-based approaches to mapping lesion-behavior correlations in brain-injured populations are increasingly popular, and have the potential to leverage image analysis methods drawn from functional magnetic resonance imaging. However, power is a major concern for these studies, and is likely to vary regionally due to the distribution of lesion locations. Here, we outline general considerations for voxel-based methods, characterize the use of a nonparametric permutation test adapted from functional neuroimaging, and present methods for regional power analysis in lesion studies.

Neuroanatomical dissociation for taxonomic and thematic knowledge in the human brain.

It is thought that semantic memory represents taxonomic information differently from thematic information. This study investigated the neural basis for the taxonomic-thematic distinction in a unique way. We gathered picture-naming errors from 86 individuals with poststroke language impairment (aphasia). Error rates were determined separately for taxonomic errors (“pear” in response to apple) and thematic errors (“worm” in response to apple), and their shared variance was regressed out of each measure. With the segmented lesions normalized to a common template, we carried out voxel-based lesion-symptom mapping on each error type separately. We found that taxonomic errors localized to the left anterior temporal lobe and thematic errors localized to the left temporoparietal junction. This is an indication that the contribution of these regions to semantic memory cleaves along taxonomic-thematic lines. Our findings show that a distinction long recognized in the psychological sciences is grounded in the structure and function of the human brain.

Direct comparison of fluorodeoxyglucose positron emission tomography and arterial spin labeling magnetic resonance imaging in Alzheimer's disease

The utility of fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging in Alzheimers disease (AD) diagnosis has been well established. Recently, measurement of cerebral blood flow using arterial spin labeling magnetic resonance imaging (ASL‐MRI) has shown diagnostic potential in AD, although it has never been directly compared with FDG‐PET.

Cortical effects of bromocriptine, a D-2 dopamine receptor agonist, in human subjects, revealed by fMRI.

Studies of human subjects performing cognitive tasks on and off dopaminergic drugs have suggested a specific role of dopamine in cognitive processes, particularly in working memory and prefrontal “executive” functions. However, the cortical effects of these drugs have been poorly understood. We used functional magnetic resonance imaging (fMRI) to examine both task‐specific and general changes in cortical activity associated with bromocriptine, a selective agonist for D‐2 dopamine receptors. Bromocriptine resulted in task‐specific modulations of task‐related activity in three cognitive tasks. Across tasks, the overall effect of the drug was to reduce task‐related activity. We also observed drug effects on behavior that correlated with individual differences in memory span. We argue that bromocriptine may show both task‐specifc modulation and task‐general inhibition of neural activity due to dopaminergic neurotransmission. Hum. Brain Mapping 12:246–257, 2001.

Towards effective and rewarding data sharing.

Recently issued NIH policy statement and implementation guidelines (National Institutes of Health, 2003) promote the sharing of research data. While urging that “all data should be considered for data sharing” and “data should be made as widely and freely available as possible” the current policy requires only high-direct-cost (>US